Chemical Weapons:
Nerve Agents

You may have read newspaper or magazinearticles about the possible use of chemicals during a war or a terroristattack. Many of these chemicals affect the nervous system and aretherefore called nerve agents. Nerve agents aresimilar to insecticides and they can be deadly if people are exposed tothem. Unfortunately, this has already happened. On March 20, 1995,twelve people were killed and over 5,000 were injured when a nerve gascalled "sarin" was released in the Tokyo subwaysystem. People may have also been exposed to nerve agents during the recent conflict in the Middle East. It ispossible that many countries have access to these dangerous weapons andfuture human exposure to these chemicals is possible.

History

masknopestMost nerve agents belong to a group ofchemicals called "organophosphates". The first of these chemicals wasmade in 1854 and was originally developed to be used to control insectsandsave crops. The first nerve agent (called "Tabun" or "GA") for militaryuse was made in Germany in 1936. Another nerve agent, "sarin" or "GB",was made in 1938 and "Soman" or "GD" was made in 1944. It appearsthat thesenerve agents were not used by the Germans duringWorld War II. However, it has been estimated that the Germans hadstockpiles of tons of both Tabun and Sarin. The United States and Russiacontinued producing and stockpiling these nerve agents after the War. Inthe 1950's another nerve agent, "VX", was produced in England.

NameFirst Made
(Year)		LethalDose
Breathing (mg*min/m3)		Lethal Dose
Skin(mg)
Tabun(GA)1936150-4001,000-1,700
Sarin(GB)193875-1001,000-1,700
Soman (GD)194435-5050-100
VX1952106-10
There are several less common nerveagents: GE, GF, VE, VG and VM

Breathing a lethal dose of these chemical can kill in 15 minutes; a lethal dose on the skin can kill in only 1-2 minutes!! To get anidea of how deadly these chemicals are, do the math.

1 kilogram = 1,000 gm = 2.2 lbs   1 gm  =   1,000 mg = 0.0022 lbs   10 mg = 0.000022 lbs
10 mg (0.000022 lbs) is not much more than a single grain of rice!!

Nerve agents are clear and colorless and may have no odor or a faint,sweetish smell. They are all extremely dangerousand they can enter the body through the air or on contact with the skin.They can be released using bombs, missiles, spray tanks, rockets and landmines. VX is the most deadly and Tabun is the least deadly (althoughstill very hazardous). Nerve agents are more dense than air so they areespecially dangerous to people in low areas. 

Method of Action
Acetylcholine is a common neurotransmitter found in the central andperipheral nervous system.  When acetylcholine is released from an axonterminal, it moves across the synaptic cleft to bind to a receptor on theother side of the synapse (on the post-synaptic membrane).  In theperipheral nervous system, acetylcholine is located at the"neuromuscular junction" where it acts to control muscular contraction.Acetylcholine is also used in the autonomic nervoussystem.  The action of acetylcholine is stopped by an enzyme called"acetylcholinesterase" (AChE).
Nerve agents bind to part of the AChE molecule.  Thismakes the AChE inactive and blocks theaction of AChE.  Therefore,
 
  1. there is no way to stop the action of acetylcholine
  2. acetylcholine builds up at the synapse.
  3. acetylcholine continues to act.
The Acetylcholine Synapse
NormalTransmission ofAcetylcholine
ACh = Acetylcholine
E = Acetylcholinesterase
  1. ACh is released at the axon terminal.
  2. ACh crosses the synaptic cleft.
  3. ACh binds with a receptor on the post-synapticmembrane.
  4. AChE (E) stops the action of ACh. 
Transmission with Nerve AgentPoisoning
ACh = Acetylcholine
E = Acetylcholinesterase
NA = Nerve Agent
  1. ACh is released at the axon terminal.
  2. ACh crosses the synaptic cleft.
  3. ACh binds with a receptor on the post-synapticmembrane.
  4. Nerve agents (NA) block the ability of AChE to stop the action of ACh.
  5. ACh continues to work and more ACh builds up in the synapse.
Symptoms of Nerve Agent Poisoning
Nerve agents attack all synapses that use acetylcholine as aneurotransmitter...this means both the central and peripheral nervoussystems are affected.  Symptoms of nerve agent poisoning include:
Neuromuscular EffectsAutonomic Nervous
SystemEffects		Central Nervous
SystemEffects
  • Twitching
  • Weakness
  • Paralysis
  • Respiratory failure
  • Reduced Vision
  • Small pupil size
  • Drooling
  • Sweating 
  • Diarrhea
  • Nausea
  • Abdominal pain
  • Vomiting
  • Headache
  • Convulsions
  • Coma
  • Respiratory arrest
  • Confusion
  • Slurred speech
  • Depression
  • Respiratorydepression
 
Treatment for Nerve Agent Exposure
 Immediate treatment of personwho has been exposed to a nerve agent exposure includes a complete washingof the eyes and skin with water.  A diluted (5%) bleach solution shouldalso be applied to the skin if possible.
Two drugs, atropine and pralidoxime chloride, have been used as antidotesfor nerve agent poisoning.  Atropine works by blocking one type ofacetylcholine receptor so that the acetylcholine that is already in thesynapse cannot work.  Pralidoxime works by blocking the binding of thenerve agent to the AChE.  Both of these drugs were issued to US troopsduring the Persian Gulf War in the form of an antidote kit called theMark I.  Diazepam (Valium) may be used to reduce convulsions andseizures brought on by exposure to nerve agents.
Effects of Atropine
Effect of Atropine on the Transmission ofAcetylcholine in the presence of a nerve agent
ACh = Acetylcholine
E = Acetylcholinesterase
  1. ACh is released at the axon terminal.
  2. ACh crosses the synaptic cleft.
  3. ACh binds with a receptor on the post-synapticmembrane.
  4. Nerve agents (NA) block the ability of AChE to stop the action of ACh.
  5. Atropine blocks the receptor so that ACh cannot work.  Note thatthere is NO direct effect on the nerve agent orAChE.
 
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More on the Sarin attack in Tokyo:
More on possible exposure of US troops to NerveAgents:
  • Potential exposure toSarin in Iraq 
  • DoDSays 98,910 Exposed to Low Levels of Nerve Agent
  • FactSheet on possible exposure of troops to nerve agents
  • Inquiry into demolition of Iraq ammunition
  • M8A1 AutomaticChemical Agent Alarm
  • The PersianGulf Experience and Health - from the National Institutes of Health
  • Possible causeof Gulf War Syndrome - from the American Psychological AssociationMore on disposal of Chemical Agents:
    More on Nerve Agents:
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